This Article Full Text Full Text (PDF) All Versions of this Article: 35/2/596    most recent 01.STR.0000113691.32026.06v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Costa, C. Articles by Calabresi, P. Search for Related Content PubMed PubMed Citation Articles by Costa, C. Articles by Calabresi, P. Related Collections Neuroprotectors Animal models of human disease Energy metabolism Ischemic biology - basic studies Ion channels/membrane transport

(Stroke. 2004;35:596.)
© 2004 American Heart Association, Inc.

Original Contributions

Coactivation of GABA_A and GABA_B Receptor Results in Neuroprotection During In Vitro Ischemia

Cinzia Costa, MD; Giorgia Leone, MD; Emilia Saulle, MD; Francesco Pisani, MD; Giorgio Bernardi, MD Paolo Calabresi, MD

From Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata, Rome (C.C., G.L., E.S., G.B., P.C.); Dipartimento di Neuroscienze, Psichiatria e Anestesiologia Università di Messina, Messina (F.P.); and IRCCS, Fondazione Santa Lucia, Rome (C.C., G.L., E.S., G.B., P.C.), Italy.

Correspondence to Dr Paolo Calabresi, Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata, Via Montpellier 1, Rome 00133, Italy. E-mail calabre{at}uniroma2.it

Background and Purpose— The possible neuroprotective effect of endogenous -aminobutyric acid (GABA) on the irreversible electrophysiological changes induced by in vitro ischemia on striatal neurons was investigated. In particular, the aim of the study was the characterization of the neuroprotective action of 2 antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA transaminase.

Methods— Extracellular field potential recordings were obtained from rat corticostriatal slice preparations. In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose was omitted and oxygen was replaced with N₂.

Results— An irreversible loss of the field potentials recorded from striatal neurons was observed after 10 minutes of ischemia in control solution. Conversely, tiagabine and vigabatrin partially prevented the ischemia-induced field potential loss. Surprisingly, both GABA_A and GABA_B receptor antagonists blocked these effects. Accordingly, neuroprotection could be obtained only when GABA_A and GABA_B receptor agonists were coapplied, but not when a single agonist was given in isolation.

Conclusions— Antiepileptic drugs targeting GABAergic transmission can exert neuroprotective effects against ischemia by increasing endogenous GABA levels and via the activation of both GABA_A and GABA_B receptors.

Key Words: anticonvulsants • corpus striatum • electrophysiology • ischemia • receptors, GABA

This article has been cited by other articles:

				C. Costa, V. Belcastro, A. Tozzi, M. Di Filippo, M. Tantucci, S. Siliquini, A. Autuori, B. Picconi, M. G. Spillantini, E. Fedele, et al. Electrophysiology and Pharmacology of Striatal Neuronal Dysfunction Induced by Mitochondrial Complex I Inhibition J. Neurosci., August 6, 2008; 28(32): 8040 - 8052. [Abstract] [Full Text] [PDF]

				C. Costa, G. Martella, B. Picconi, C. Prosperetti, A. Pisani, M. Di Filippo, F. Pisani, G. Bernardi, and P. Calabresi Multiple Mechanisms Underlying the Neuroprotective Effects of Antiepileptic Drugs Against In Vitro Ischemia Stroke, May 1, 2006; 37(5): 1319 - 1326. [Abstract] [Full Text] [PDF]